The proposed studies are designed to investigate three aspects of lipoprotein removal mechanism. The first aspect is designed to investigate further the kinetics of the lipoprotein lipase reaction which represents the initial step in the assimilation of chylomicrons and VLDL and which leads to the production of a cholesterol rich remnant lipoprotein. These experiments will include studies of purified LPL from normal subjects and from patients with hyperlipidemias. The second aspect is designed to investigate the influence of the chemical composition of the lipoprotein substrate on the rate and kinetic pattern of the lipoprotein lipase reaction. Normal and abnormal lipoproteins from patients will be examined. A new agarose column technique for examining lipoprotein spectra will greatly aid in the isolation of abnormal species of lipoproteins. The third aspect is designed to investigate the further metabolism of the cholesterol rich remnant lipoproteins. In vivo studies will give information on the rates of removal and lipoprotein interconversions of constituents of the remnant lipoproteins. The influence of cholesterol feeding on the nature of the remnant and on its removal will be determined. In vitro studies with isolated liver cells will provide more information about the mechanism of interaction of constituents of the remnant lipoproteins with the liver. The influence of cholesterol feeding on rate-limiting reactions in the removal of cholesterol from the remnants will be examined.